Title | Blood-Based ATN Biomarkers of Alzheimer's Disease: A Meta-Analysis. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Koychev, I, Jansen, K, Dette, A, Shi, L, Holling, H |
Journal | J Alzheimers Dis |
Volume | 79 |
Issue | 1 |
Pagination | 177-195 |
Date Published | 2021 |
ISSN | 1875-8908 |
Keywords | Alzheimer Disease, Amyloid beta-Peptides, Humans, Neurodegenerative Diseases, Neurofibrillary Tangles, Neurofilament Proteins, Peptide Fragments, Phosphorylation, Plaque, Amyloid, tau Proteins |
Abstract | BACKGROUND: The Amyloid Tau Neurodegeneration (ATN) framework was proposed to define the biological state underpinning Alzheimer's disease (AD). Blood-based biomarkers offer a scalable alternative to the costly and invasive currently available biomarkers. OBJECTIVE: In this meta-analysis we sought to assess the diagnostic performance of plasma amyloid (Aβ40, Aβ42, Aβ42/40 ratio), tangle (p-tau181), and neurodegeneration (total tau [t-tau], neurofilament light [NfL]) biomarkers. METHODS: Electronic databases were screened for studies reporting biomarker concentrations for AD and control cohorts. Biomarker performance was examined by random-effect meta-analyses based on the ratio between biomarker concentrations in patients and controls. RESULTS: 83 studies published between 1996 and 2020 were included in the analyses. Aβ42/40 ratio as well as Aβ42 discriminated AD patients from controls when using novel platforms such as immunomagnetic reduction (IMR). We found significant differences in ptau-181 concentration for studies based on single molecule array (Simoa), but not for studies based on IMR or ELISA. T-tau was significantly different between AD patients and control in IMR and Simoa but not in ELISA-based studies. In contrast, NfL differentiated between groups across platforms. Exosome studies showed strong separation between patients and controls for Aβ42, t-tau, and p-tau181. CONCLUSION: Currently available assays for sampling plasma ATN biomarkers appear to differentiate between AD patients and controls. Novel assay methodologies have given the field a significant boost for testing these biomarkers, such as IMR for Aβ, Simoa for p-tau181. Enriching samples through extracellular vesicles shows promise but requires further validation. |
DOI | 10.3233/JAD-200900 |
Alternate Journal | J Alzheimers Dis |
PubMed ID | 33252080 |
Grant List | / MRC_ / Medical Research Council / United Kingdom / / Department of Health (NIHR) / |
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